Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22.

MedLine Citation:

PMID:
22961652
Owner:
NLM
Status:
Publisher

Abstract/OtherAbstract:

Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by γδ T cells, NK cells and lymphoid tissue inducer (LTi) cells. Th17 cells develop from precursor cells after TCR stimulation in the presence of TGF-β, IL-6 and IL-23. In contrast, a subset of γδ T cells ("γδT17") is committed for fast IL-17 production already in the thymus; however, γδ T cells can also produce IL-17 after prolonged in vitro stimulation via their γδ TCR plus IL-23. Here, we show that γδ T-, LTi- and NKT- cells differ extensively from Th17 cells in their signalling requirements for the generation of IL-17A and IL-22. While production of these cytokines by Th17 cells totally depends on the transcription factor Interferon-Regulatory-Factor 4 (IRF4), IRF4 is irrelevant in the other cell types. As for γδ T cells, this finding pertains to both thymic commitment and prolonged in vitro culture. Furthermore, IL-17A-producing γδ T cells accumulate in the CNS of IRF4 deficient (Irf4(-/-) ) mice during experimental autoimmune encephalomyelitis. IL-17A-producing wt and Irf4(-/-) γδ T cells equally express CCR6 and lack CD27. The underlying IRF4 independent pathway partially involves STAT3 during in vitro stimulation.